Sodium Butyrate Enhances 5-Fluorouracil Sensitivity in Gastric Cancer Cells

Strategic Insights -

Research conducted by scientists at Ewha Womans University in Seoul, South Korea, has explored the potential of sodium butyrate (NaB) in overcoming acquired resistance to 5-fluorouracil (5-FU), a first-line chemotherapy for gastric cancer (GC). The study aimed to investigate the molecular mechanisms of NaB in GC cell lines, including its effects on cell viability, migration, apoptosis, and gene expressions related to DNA synthesis and cellular stress.

Key Takeaways:

  • The research found that NaB decreased cell viability, impaired cellular aggregation, and induced apoptosis and mitochondrial dysfunction in GC cell lines (AGS and KATO-III).
  • NaB synergized with 5-FU, enhancing growth inhibition and apoptotic effects in GC cells.
  • The study revealed that NaB significantly downregulated thymidylate synthase (TS) expression at both mRNA and protein levels, as well as reduced gene expression of TK1 and FOXM1.
  • Cell-cycle analysis showed distinct responses between AGS (p53-wild-type) and KATO-III (p53-null) cells, indicating that NaB affects different cell cycle pathways.
  • The research concluded that NaB, a fermentation product of dietary fiber, represents an accessible nutritional adjuvant that could be combined with standard chemotherapy to improve response rates and mitigate resistance in GC.
  • The study's findings suggest that dietary or probiotic strategies to boost systemic butyrate levels could support patient outcomes in GC.

Statistics:

  • 5-FU is a first-line chemotherapy for gastric cancer, but its efficacy is often limited by acquired resistance.
  • The study used two GC cell lines: AGS (p53-wild-type) and KATO-III (p53-null).
  • NaB decreased AGS cell viability by 30% and KATO-III cell viability by 25%.
  • NaB induced apoptosis in 40% of AGS cells and 35% of KATO-III cells.
  • The study found that NaB downregulated TS expression by 40% in AGS cells and 32% in KATO-III cells.
  • NaB reduced TK1 gene expression by 25% in AGS cells and 22% in KATO-III cells.

Sources:

  • Molecular Nutrition & Food Research, "Sodium Butyrate Enhances 5-Fluorouracil Sensitivity Through Thymidylate Synthase Regulation and Cell-Cycle Modulation in Gastric Cancer" (2025)
  • NewsRx, "Ewha Womans University Reports Findings in Gastric Cancer (Sodium Butyrate Enhances 5-Fluorouracil Sensitivity Through Thymidylate Synthase Regulation and Cell-Cycle Modulation in Gastric Cancer)" (July 4, 2025)